Recent developments in magnetic resonance tomography (MRT) and [nuclear] magnetic resonance (NMR) spectroscopy using polarized noble gases have many applications in medicine, physics, and in the physical sciences. Noble gas nuclei may be polarized by optical pumping using alkali metal atoms, as described by Happer et al in Phys. Rev. A, 29, 3092 (1984).
The concept of optical pumping encompasses the method developed by Kastler, in which the occupation numbers of specific energy states are significantly increased with respect to the equilibrium state by irradiation of light into matter. By use of optical pumping, the relative occupation numbers of energy levels in atoms, ions, molecules, and solids may be changed, and ordered states may be produced. The occupation density of the optically pumped state differs markedly from the thermal occupation probability of the state according to the Boltzmann distribution. By optical pumping of Zeeman levels it is possible, for example, to achieve a parallel configuration of the magnetic moments of the electrons or atomic nuclei.
In practice, the alkali metal atom rubidium is typically used in the presence of the noble gases helium and nitrogen. In this manner it is known to achieve a nuclear spin polarization of approximately 20% for 129Xe, for example. Such a nuclear spin polarization is approximately 100,000 times larger than the equilibrium polarization in clinical magnetic resonance tomography at 1 T and 300 K. The associated drastic increase in the signal-to-noise ratio is the reason that new application options are in demand in medicine, science, and technology.
The term “polarization” is understood to mean the degree of alignment (ordering) of the spins of atomic nuclei, electrons, or photons. For example, 100% polarization means that all nuclei or electrons are identically oriented. A magnetic moment is associated with the polarization of nuclei or electrons.
Hyperpolarization refers to a polarization level of nuclear or electron spins that is greater than the degree of thermal polarization of the spins in a given magnetic field at room temperature.
Hyperpolarized noble gases are used as contrasting agents or for NMR spectroscopy. For example, hyperpolarized 129Xe is inhaled by or injected into a person. The polarized xenon accumulates in the brain 10 to 15 seconds later. The distribution of the noble gas in the brain is determined by use of magnetic resonance tomography, and the results are used for further analyses.
The selection of the noble gas depends on the particular application. 129Xe has a large chemical shift. When xenon is adsorbed onto a surface, for example, the resonance frequency of the xenon is significantly altered. In addition, xenon is soluble in lipophilic liquids. Xenon is used when such characteristics are desired.
The noble gas helium has very low solubility in liquids. Therefore, the isotope 3He is routinely used when cavities are involved. The human lung represents an example of such a cavity.
Some noble gases have valuable properties other than those stated above. For example, the isotopes 83Kr, 21Ne, and 131Xe have a quadrupole moment that is of interest, for example, for experiments in basic research or surface physics. However, these noble gases are very costly, which makes them unsuitable for applications that use large quantities.
It is known from Driehuys et al (Appl. Phys. Lett. (1996), 69, 1668) to polarize noble gases in a polarizer in the following manner.
Starting with a gas supply, a gas stream composed of a mixture of 129Xe, 4He, and N2 in an Rb container is enriched with Rb vapor and passed through a pump cell. Circularly polarized light, i.e., light in which the angular momentum or the photon spin is aligned in the same direction, is provided by a laser. In the pump cell the Rb atoms as a pumpable species are optically pumped longitudinally with respect to a magnetic field by means of the laser beam (λ˜795 nm, Rb D1 line), thereby polarizing the electron spins of the Rb atoms. The angular momentum of the photons is transferred to free electrons of alkali metal atoms. The spins of the electrons of the alkali metal atoms thus have a large deviation from thermal equilibrium. The alkali metal atoms are consequently polarized. Collision of an alkali metal atom with a noble gas atom causes the polarization of the electron spin to be transferred from the alkali metal atom to the noble gas atom, resulting in a nuclear spin-polarized noble gas. The polarization of the electron spin of the alkali metal atoms produced by the optical pumping of alkali atoms is thus transferred from alkali electrons to the nuclear spin of the noble gases by spin exchange, as first demonstrated by Bouchiat on the Rb/3He system.
From WO 1999/008766 it is known to use, in addition to a first optically pumpable alkali metal, an auxiliary alkali metal as a second polarizable species. The optically pumped alkali metal species transfers the electron spin polarization to the auxiliary alkali metal, thereby more effectively and rapidly transferring the alkali polarization to the noble gas nuclei, for example 3He.
Alkali metal atoms are used because they have a large optical dipole moment that interacts with the light. The alkali metal atom also has one free electron, thus preventing disadvantageous interactions from occurring between two or more electrons per atom.
Cesium, which is superior to rubidium for achieving the above-referenced effects, might be considered as a well-suited alkali metal atom. However, lasers matched to the optical wavelength of Cs and having sufficient power necessary for polarization of xenon by cesium are not prevalent on the market, compared to the corresponding lasers for Rb.
In order to utilize as many photons as possible in the use of broadband high-power semiconductor lasers, pressures of several atmospheres are used in the optical pumping of noble gases. Thus, the optical pumping of alkali metal atoms differs, depending on the type of the noble gas to be polarized.
For polarization of 129Xe, a gas mixture under a pressure of approximately 7 to 10 bar is continuously or semicontinuously passed through a cylindrical glass cell. The gas mixture is composed of 94% 4He, 5% nitrogen, and 1% xenon. The flow rate of the gas mixture is typically 1 cm per second.
Hyperpolarized nuclear and electron spins relax more or less rapidly as a function of their environment. A distinction is made between the longitudinal T1 relaxation time (T1 time for short), referred to as spin lattice relaxation of adjacent spins, and the transverse T2 relaxation time, referred to as spin-spin relaxation.
In the case of polarization of 3He, the pressure required in the polarizer is produced by the 3He itself since the electron spin relaxation rate of Rb—3He collisions is small. This is not is the case for spin exchange pumping of Rb—129Xe, for which reason the pressure is produced by an additional buffer gas such as 4He. Various requirements are imposed on the polarizer as the result of the differing relaxation and spin exchange rates.
Thus, for 3He the nuclear spin polarization build-up times are in the range of hours. However, since the rubidium spin decomposition rate for rubidium-3He collisions is also relatively small, in this case high 3He pressures (>5 bar) may be used.
For 129Xe, on the other hand, the nuclear spin polarization build-up times are between 20 and 40 seconds on account of the larger effective spin exchange cross-sectional area. Due to the very large rubidium electron spin relaxation rate for rubidium-xenon collisions, during the optical spin exchange pumping the xenon partial pressure can only slightly exceed 100 mbar in order to maintain a sufficiently high rubidium polarization. For this reason, in such polarizers 4He is used as a buffer gas for line broadening.
The polarizer may be designed as a flow polarizer for polarizing 129Xe, for example, or may be provided with a sealed sample cell for 3He, for example.
In a flow polarizer, the gas mixture initially flows through a vessel, referred to hereinafter as a “supply vessel,” in which a certain quantity of Rb is present. The supply vessel containing the rubidium together with the connected glass cell is heated to approximately 100 to 170 degrees Celsius. At these temperatures the rubidium is vaporized. The concentration of the vaporized rubidium atoms in the gaseous phase is determined by the temperature in the supply vessel. The gas stream transports the vaporized rubidium atoms from the supply vessel into a cylindrical sample cell, for example. A laser that provides a high-power, circularly polarized light and having a power rating of approximately 50-100 watts continuously irradiates the sample cell in an axial direction, i.e., in the direction of flow, and optically pumps the rubidium atoms in a highly polarized state. The wavelength of the laser must be matched to the optical absorption line of the rubidium atoms (D1 line).
In other words, in order to optimally transfer the polarization of light to an alkali metal atom, the frequency of the light must match the resonance frequency of the optical transition.
The sample cell is located in a static magnetic field Bo of approximately 10 gauss, which is generated by coils, in particular by a Helmholtz coil pair. The direction of the magnetic field extends parallel to the cylindrical axis of the sample cell, i.e., parallel to the beam direction of the laser. The magnetic field is used to guide the polarized atoms. The rubidium atoms that are optically highly polarized by the laser light collide in the glass cell with the xenon atoms, among other species, and transfer their polarization to the xenon atoms.
At the outlet of the sample cell, the rubidium deposits on the wall due to its high melting point compared to the melting points of the other gases. The polarized xenon or the residual gas mixture is conveyed from the sample cell into a freezer unit, which is composed of a glass flask immersed at one end in liquid nitrogen. The glass flask is also situated in a magnetic field having an intensity of >1000 gauss. The highly polarized xenon gas deposits as ice on the inner glass wall of the freezer unit.
The flow rate in the entire system may be controlled via a needle valve and measured with a measuring instrument.
If the increase in the flow rate is excessive, there is not enough time to transfer the polarization from the rubidium atoms to the xenon atoms, resulting in low polarization. If the flow rate is too low, too much time elapses until the desired quantity of highly polarized xenon is frozen. The polarization of the xenon atoms therefore decreases as the result of relaxation in the Xe ice. The relaxation of the xenon atoms is greatly retarded by freezing, as well as by a strong magnetic field to which the freezer unit is exposed. Therefore, after the polarization the noble gas xenon must be frozen as rapidly as possible with minimization of loss. Although the relaxation cannot be completely prevented by freezing, at 77 K there is a period of approximately 1 to 2 hours before the xenon polarization has decreased so greatly that the initially highly polarized gas can no longer be used.
A certain amount of energy is required to polarize a single free alkali metal atom. The required energy corresponds to the resonance frequency for elevating the free electron of the alkali metal atom from a ground state to an excited state. In order to optimally transfer the energy from a laser to the alkali metal atom, the frequency of the light from the laser must be matched to the resonance frequency of the alkali metal atom. Some lasers emit light within a specific frequency spectrum. Thus, a distribution of frequencies, not a single frequency, is involved. The available spectrum of a laser is characterized by the line width. For cost-effective polarization of alkali metal atoms, broadband semiconductor lasers are provided whose frequency and line width are matched to the resonance frequency, i.e., the optical line width, of the alkali metal atom.
To enable better transfer of the energy from a laser to alkali metal atoms, collision partners are provided for the alkali metal atoms during the polarization. 4He atoms in particular are used as collision partners. The optical line width of an alkali metal atom is broadened as a result of the interaction, i.e., the collisions, with the helium atoms. The broader this atomic spectrum, the greater the spectral width, and therefore the lower the cost, of the lasers that can be used.
The number of collisions between an alkali metal atom and a collision partner such as 4He increases with increasing pressure. For 4He, for example, the broadening of the optical line width of the alkali metal atom is proportional to the pressure of the helium gas. In addition, 4He has the valuable characteristic that it has a minimal destructive influence on the polarization of the alkali metal atoms. For the polarization of 129Xe, therefore, a gas mixture is routinely used that is composed of 94% 4He and has a pressure of approximately 10 bar.
The laser known from the prior art, having a power of 100 watts for the hyperpolarization of Rb electrons, is a glass fiber-coupled diode laser having a typical spectral width of 2 to 4 nanometers. At a gas pressure of 10 bar, the line width of the optical transition of rubidium atoms is broadened to approximately 0.3 nanometers. Thus, in the present rubidium-xenon polarization, in which high-power diode lasers are used for optical pumping which typically have a line width of 2 nanometers, only a fraction of the laser light is utilized.
The partial pressure of 4He in the gas mixture is less than or equal to 10 bar. This is very high compared to the other partial pressures (xenon and nitrogen). As a result, polarized alkali metal or noble gas atoms rarely reach the inner wall of the glass cell, where they lose their polarization due to interaction with the paramagnetic centers, for example. Thus, with increasing partial pressure of the 4He, the lower the probability that polarized atoms disadvantageously collide with the inner wall of the cell.
A polarized alkali metal atom such as rubidium, for example, is able to generate fluorescent radiation. When such radiation is intercepted by another polarized alkali metal atom, this capture results in depolarization of the alkali metal atom. The nitrogen used in the gas mixture for the polarization of noble gases is used to hinder the fluorescent light and thus the capture of radiation. The element nitrogen in the gas mixture, the same as for xenon, has a low partial pressure. This partial pressure is typically approximately 0.1 bar.
For heavy noble gas atoms such as xenon atoms, collision with the alkali metal atoms causes intense relaxation of the polarization of the alkali metal atoms. To keep the polarization of the alkali metal atoms as high as possible during optical pumping, the partial pressure of the xenon gas in the gas mixture must be correspondingly low. Even for a xenon partial pressure of 0.1 bar in the gas mixture, a laser power of approximately 100 watts is required to achieve approximately 70% polarization of the alkali metal atoms in the entire sample volume.
According to the prior art, a gas volume of appropriate composition is injected into a cylindrical sample cell. The light from the laser that produces the polarization is absorbed in the sample cell. The pump beam irradiates the sample cell in the direction of flow of the mixture, which includes the optically pumpable species and the atomic nuclei to be hyperpolarized, parallel to the magnetic field.
In contrast, it is known from US 2002/0107439 A1 to irradiate the sample cell with laser light in counterflow to the flowing mixture.
In biological systems, short longitudinal T1 times of the noble gas nuclei in the blood, as well as the low solubility in aqueous solutions, severely limit the use of hyperpolarized noble gases. For example, for medical applications it has not been possible thus far to transport 129Xe with sufficient polarization density into the brain, since the T1 times in the blood are short (˜10 s), and the transport technology for this purpose is very complex or has not been developed at all. The same applies for the other noble gases under discussion.
DE 102 38 637 A1 describes a method for producing nuclear spin-polarized liquids. A polarized Li atomic beam is generated by optical pumping or by use of a Stern-Gerlach apparatus, and is directed onto the liquid.
However, it is disadvantageous that the maximum achievable density of lithium atoms in the atomic beam is only 1013 cm−3. In addition, the method functions only at low pressures <10−3 mbar. This greatly limits the total number of polarized Li atoms or ions that are produced (<1015).
For use of hyperpolarized 6Li and also 7Li in the life sciences and material sciences, the production and storage of large quantities of approximately 1019 hyperpolarized Li+ ions or Li atoms is desirable.